WHO support and Technical Assistance _

In-Vitro Diagnostics

Joint UNICEF, UNFPA & WHO Meeting with

Manufacturers and suppliers

UN City, Copenhagen, Denmark

24-27 September 2018

Dr Gaby Vercauteren

Senior Adviser, Regulatory Systems Strengthening Team

Regulation of Medicines and other Health Technologies

Copenhagen, Denmark 24 – 27 September 2018 1

2 Copenhagen, Denmark 18-21 September 2017

– The context

– Eligibility for technical assistance

– Principles & priorities for technical assistance

– Types of technical assistance and some data

– Past & future activities

Outline

The context

Every year, hundreds of millions of US dollars’ worth of

IVDs and medicines are purchased for distribution in

resource-limited countries

IVDs play a critical role in ensuring blood safety,

surveillance, diagnosis and treatment initiation

and monitoring

IVDs save lives, reduce suffering and improve health, but

only when they are of good quality, safe, effective,

available, affordable, acceptable and properly used

Copenhagen, Denmark 24 – 27 September 2018 3

WHO Prequalification – access to the global market

Prequalification listing linked to

• UN agencies procurement (WHO, UNICEF, UNDP,

UNFPA)

• The Global Fund QA policy

• MSF

• Strong collaboration with USG (USAID, CDC)

• National procurement / tendering specs

Range of products from which procurers can select

Copenhagen, Denmark 24 – 27 September 2018 4

Prequalification scope

HIV G6PD

malaria

HPV HCV

HBV

Cholera Syphilis

Expansion of PQDx scope over time

PQ eligibility

consultation – SAGE-IVD

6

Globalised industry sectors with outsourced production

Rapid emergence of new technologies

Increasing expectations on quality, safety and performance

Increasing pressure on human resources and increased

workload for regulators

Easy to operate tests/methods facilitate near patient testing,

hard-to-reach populations, non-lab environments

Changing IVDs global market trends

Copenhagen, Denmark 24 – 27 September 2018 7

PQ in a regulatory framework

Pre-market

Post-market

perfor

mance quality safety

Pre-2008

2008 - 2014

Post-2014

Changes

perfor

mance quality safety

reliance

WHO PQDx regulatory framework

Copenhagen, Denmark 24 – 27 September 2018 9

ISO and EN standards

GHTF / IMDRF

guidance documents

CLSI guidance

documents

PQ requirements

Prequalification: decision

Final prequalification outcome depends on:

• Results of dossier assessment and acceptance of action plan

• Results of inspection(s) and acceptance of action plan

• No level 5 nonconformities outstanding for either dossier or for

inspection

• Meeting the acceptance criteria for the laboratory evaluation

WHO PQDx Public Report is posted on WHO website and product is

added to the list of WHO prequalified products

Product is then eligible for WHO and UN procurement

What does PQ do differently to

GHTF/IMDRF

Requirements are based on the same set of standards – PQ is

aligned with internationally accepted practice BUT

Assess products' regulatory versions intended for the global market

• Where a stringently reviewed versions exist, they are often not supplied to

the global market – RoW versions differ from stringently assessed version

in Mx site, QC, labelling, key suppliers, composition, intended use etc.

Review aspects of particular relevance for resource-limited settings

• Risk assessment, stability, flex studies, labelling, training and support

network

• Take into account environment and user skills

What do we mean to regulate?

TESTS TESTING

? ? ? ? ?

POTENTIAL POINTS OF REGULATION

Background_ Rationale

Lessons from PQDx

Dossier submissions are improving, some still

substandard

– Unclear product identification

– Instruction for Use not conform requirements

– Insufficient control over key suppliers

– Quality control of lots

– Stability testing

– Performance studies

• Lack of evidence of performance in the intended

use setting

Copenhagen, Denmark 24 – 27 September 2018 13

Background_ Rationale

Lessons from PQDx

A portion of inspections have shown critical

nonconformities

– Ineffective quality management system

– Unsuitable facilities

– Lack of/ insufficient quality control of key product

components

– Traceability issues; from raw materials to lot release

– Inadequate documentation and procedures to verify

QC for lot release

– Inadequate procedures to handle customer

complaints

Copenhagen, Denmark 24 – 27 September 2018 14

Background_ Rationale

Lessons from PQDx

Lab evaluations

– Instructions for use_ often poor

– interpretation of results and reading times

– HIV RDTs lot to lot variation generally OK

– Customer service_ product identification

Alerts_ Recalls

– Manufacturers may not be well prepared to act

– Retained samples for a case of complaint " product

failure"

– Improve streams between_ user_ procurer _ Mx

Copenhagen, Denmark 24 – 27 September 2018 15

Background_ Rationale

Lessons from Mapping regulatory capacity for medical

devices _including IVDs

Regulation of IVDs is weak or lacking in many countries

– Africa, Asia,

– Recipient countries

– Countries with substantial manufacturing of UN

priority IVDs

Several countries have or are in the process of putting

regulations for medical devices in place

– i.e. South Africa, other African countries, India

– P.R. China is converging towards IMDRF guidance

Copenhagen, Denmark 24 – 27 September 2018 16

What do we want from you ?

Manufacturers

- IVDs of assured quality within the PQ scope to be

prequalified

- Investment in innovative IVDs adapted to LMIC countries

National regulatory authorities

- Implementation of regulation of IVDs aligned with IMDRF

- Pre- market

- Post market - So that in future WHO PQ and countries in the region

can rely on work that has been done satisfactory and

avoid duplication.

Copenhagen, Denmark 24 – 27 September 2018 17

Priorities for support & technical

assistance

Manufacturers/ Innovators of

– IVDs that are a priority and few products have been

PQ-ed

– Mx of priority IVDs that have potential, but previous

submission(s) to PQDx failed.

– Mx in stringently regulated countries_ products for the

Global market

Regulators/ Inspectorates / Notified bodies

– Countries with major production of IVDs for the global

market

• China, India, Korea

– Recipient Countries starting regulation of IVDs

Copenhagen, Denmark 24 – 27 September 2018 18

What can we do for you?

Copenhagen, Denmark 24 – 27 September 2018 19

What is the type of technical support that we

provide ?

• RSS advisory visits to manufacturers

- Gap analysis, assessement of readiness for PQ

• RSS trainings for manufacturers

- Topic specific trainings

• RSS trainings for NRAs

- Topic or function specific trainings

Copenhagen, Denmark 24 – 27 September 2018 20

RSS technical assistance

Copenhagen, Denmark 24 – 27 September 2018 21

PQDx requirements

Analyte-specific issues

Research and

development

The QMS, regulation

and certification

Types of technical assistance

Communication and advisory visits

– Gap analysis _innovators

Useful Tools

– Sample dossier_ e.g. CD4

– Training packages

– Guidance documents

Tailor made TA to Mx on specific technical issues

Training on general aspects and commonly

observed technical issues

Copenhagen, Denmark 24 – 27 September 2018 22

> Product dossier: > 3 sample dossiers (VL, EID and HIVST)

> several guidance documents to support dossier submissions > TGS1 Reference documents

> TGS2 Stability studies

> TGS3 Principles for performance studies

> TGS4 Sample dossiers

> TGS5 Product specific guidance

> TGS6 IFU

> TGS7 Flex studies

> TGS8 Specimen types

> TGS9 Test method validation

> IMDRF ToC (more granularity than STED)

> Inspections: > guidance documents

> TGS10 Quality control principles

> TGS11 Outsourcing and supplier mgt

PQDx technical guidance documents

Technical

assistance:

workshops

complemen

ting

guidance

(training

materials,

case

studies)

Set of

guidance

documents

and training

sessions to

assist

manufactur

ers

Overview of diagnostics-related Technical

Assistance and Laboratory services trainings Topics Activity Date Number trained

9 June _ am

2015

2016

2017

2018

▪ Advocacy meeting_ prequalification of Diagnostics, the importance of quality

▪ Main stakeholders meetings, manufacturers association, NACO, Un agencies representatives, CDSCO

▪ Major institutions

12-15 October

▪ NIFDC-WHO meeting PQ regulatory requirements and stability studies

▪ Commonly observed short comings in study design, analytical and clinical and stability studies, lot release testing, repositories, focus on HIV, Hepatitis B &C.

9- 11 June ▪ PQDx training Indian manufacturers ▪ Risk management and quality control for in-vitro

diagnostics

▪ PQDx observed non-conformities, detailed overview of risk management, risk analysis, risk report , risk mitigation, quality control of intermediate and final products

14 am June ▪ Advocacy meeting, ▪ Different Ministries and government officials, CDSCO, industry association

14 pm-16 June

▪ Workshop for Indian manufacturers: ▪ Regulatory requirements for performance & stability

studies for in-vitro diagnostic medical devices

▪ Commonly observed short comings in study design, analytical and clinical and stability studies, lot release testing, repositories, focus on HIV, Hepatitis B &C.

20-22 September

▪ PQDx training Chinese manufacturers ▪ Risk management and quality control for in-vitro

diagnostics

▪ PQDx observed non-conformities, detailed overview of risk management, risk analysis, risk report , risk mitigation, quality control of intermediate and final products

12-16 December

▪ Joint CFDA-WHO meeting .Dossier assessment of IVDs

▪ Exchange of information of processes and procedures , review and comparison of regulatory approaches.

8-10 August

▪ WHO training CDSCO ▪ Overview of PQ processes and procedures, dossier assessment, inspections and laboratory evaluations, Post market surveillance

26-27 October

▪ WHO meeting for Chinese manufacturers on regulatory requirements for performance & stability studies of malaria rapid diagnostic tests (IVD)

▪ Detailed overview of PQ requirements for malaria RDTs, GTS and TSS docu-ments, dossier requirements, inspections, analytical and clinical performance, requirements, Post market surveillance . participation of BMGF, China

12-14 December

▪ Joint CFDA/ WHO meeting : Dossier assessment of IVDs

▪ Update on PQ processes and procedures, and new TSS documents dossier assessment, inspections and new ISO 1348:2016 aspects post market surveillance

15-17 February

▪ India Pharma and Medical devices Forum. ▪ Advocacy and technical information sharing on prequalification of diag-nostics and implementation of the new rules. Presenting at the meeting and participating in several panel discussions and side events.

4-7 December

▪ WHO training CDSCO, inspectors ▪ PQ approaches to inspection, rating of non-conformities, inspection reports, corrective action plans

22-23 June ▪ 2nd Forum on China Biological Diagnostics ▪ Presentation on Prequalification of diagnostics and global market requirements

21-24 August

▪ WHO-CFDI training for inspectors ▪ PQ approaches to inspection, rating of non-conformities, inspection reports, corrective action plans 30

29

24

28

30

23

20

35

40

20

40

750

Planned

700

Expected outcomes

Improved quality & safety of products

Product better responding to the needs of the global market

Positive spin off effect on all products manufactured, at a site and/or

by a company

More efficient prequalification process:

– shorter timelines & higher success rate

Improved regulatory capacity in key countries

Thus :

More quality diagnostics available and accessible to

improve the health of people in low- and middle-income

countries

Copenhagen, Denmark 24 – 27 September 2018 25

Future plans

• To continue the activities, but also further

expand involvement of third parties.

• To involve more local players to expand the

reach out to local manufacturers

• India and P.R. China

• To foster regional regulatory networks for IVDs

• To build trust with PQDx and amongst each other

• Mapping of specific training needs for NRAs and

affiliated Institutions

Copenhagen, Denmark 24 – 27 September 2018 26

Contact us

Contact us by email

vercautereng@who.int

By emailing diagnostics@who.int

http://www.who.int/prequalification

Sign up to our mailing list

Check our website

Questions

Copenhagen, Denmark 24 – 27 September 2018 28